POS0104 A PHASE 2B DOUBLE-BLIND PLACEBO-CONTROLLED RANDOMIZED CLINICAL TRIAL OF SB-061, AN AGGRECAN MIMETIC, IN SUBJECTS WITH SYMPTOMATIC KNEE OSTEOARTHRITIS
Authors: A. R. Bihlet, I. Byrjalsen, K. Mundbjerg, P. Alexandersen, H. Rovsing, T. Axelsen, J. R. Andersen, A. Metnik, N. Bachtell, A. Brett, C. Christiansen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoarthritis (OA) is a chronic disease characterized by degradation of joint structures including the subchondral bone, the synovium, and cartilage. Aggrecan constitutes a major component of hyaline cartilage and plays an important role for its normal function. In OA, aggrecan is gradually lost, which together with cytokines, proteases, and circulating pro-inflammatory fragments of hyaluronic acid (HA) further accelerates tissue destruction. SB-061 is an aggrecan mimetic, composed of a backbone of chondroitin sulfate conjugated to a HA peptide coating protein. SB-061 is believed to bind HA fragments in the synovium. Hence, SB-061 acts upstream in the inflammatory cascade, thereby potentially reducing both pain as well as structural deterioration [1]. <h3>Objectives</h3> To evaluate the efficacy and safety of intra-articular injections of SB-061 in subjects with knee OA. <h3>Methods</h3> This was a randomized, placebo-controlled, double-blind phase II study comparing quarterly intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks (EudraCT No. 2019-004515-31). Eligible subjects had a Kellgren-Lawrence (KL) grade of 2 or 3 on X-ray of the target knee and a Western Ontario and McMasters Osteoarthritis Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having used any medication known to affect the joints up to 3 months prior to the study or having any other knee condition were excluded. Any use of analgesic medication was prohibited during the study, except for rescue medication (paracetamol/acetaminophen). The primary endpoint was the change from baseline (CFB) in WOMAC pain at Week 8 after first injection. Secondary endpoints were CFB in WOMAC function and total, ICOAP and the Patient Global Assessment (PGA), and 20-meter walk test. Exploratory structural endpoints included CFB in knee cartilage thickness and volume, and bone shape as measured by magnetic resonance imaging (MRI), and CFB in the radiographic minimum joint-space width (JSW). <h3>Results</h3> A total of 288 subjects were randomized to SB-061 (n= 145) or placebo (n=143), and of these 252 (87.5%) completed injections. The two groups were well-balanced in terms of the main clinical and radiographic parameters, and reflective of a typical OA clinical trial population. The primary endpoint was not met, as there was no significant difference in the CFB of the WOMAC pain score (0-50) at Week 8 between the groups (LSmean difference: 0.00, 95% CI -4.33; 4.34, p=0.999, nor at any other time point during the trial (Figure 1). Similarly, neither of the secondary endpoints of changes from baseline in WOMAC function, WOMAC total, ICOAP, PGA, and 20-meter walk test indicated any significant difference between SB-061 and placebo. There was no significant difference between groups in CFB in JSW or any of the MRI parameters. The frequency and type of adverse events was similar between groups receiving SB-061 and placebo. SB-061 was well-tolerated. <h3>Conclusion</h3> Intra-articular injections of SB-061 administered quarterly for one year in patients with knee OA was safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo. <h3>Reference</h3> [1]Hauser-Kawaguchi A, Luyt LG, Turley E. Design of peptide mimetics to block pro-inflammatory functions of HA fragments. Matrix Biology. 2019 at https://doi.org/10.1016/j.matbio.2018.01.021. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Asger Reinstrup Bihlet Employee of: Employee and shareholder in Nordic Bioscience., Inger Byrjalsen Employee of: Previous employee in Nordic Bioscience., Kamilla Mundbjerg Employee of: Employee in Nordic Bioscience Clinical Development., Peter Alexandersen Employee of: Part-time employee Nordic Bioscience Clinical Development., Helene Rovsing: None declared, Tobias Axelsen: None declared, Jeppe Ragnar Andersen Employee of: Employee and shareholder in Nordic Bioscience., Anna Metnik Employee of: Employee in Nordic Bioscience Clinical Development., Nathan Bachtell: None declared, Alan Brett Employee of: Employee and shareholder in Stryker., Claus Christiansen Employee of: Shareholder in Nordic Bioscience.